Persons with HIV and the acquired immunodeficiency syndrome (AIDS) have markedly elevated risks for developing Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), Merkel cell carcinoma (MCC), and anogenital cancers associated with human papillomavirus (HPV) infection. Importantly, people with HIV/AIDS have consistently been noted to have significantly reduced risks for breast and prostate cancers, compared to people in the general population. The primary cause of KS is infection with the KS-associated herpesvirus (KSHV, also known as human herpesvirus 8). Because KS among people with HIV/AIDS is closely tied to perturbations of immunity, which can be severe, the current study focuses on classical KS (cKS), which occurs predominantly in elderly adults in the Mediterranean area, people who have no overt immunologic abnormalities. This study builds upon a population-based case-control study conducted in Sicily to identify cofactors for both KSHV infection and for cKS among those with KSHV. KS occurs more than 100-fold more frequently and HL occurs approximately 15-fold more frequently in people with HIV/AIDS than in the general population. Collaborations with INSERM in Paris, France, are exploring the possiblity that KS and HL are a manifestation of the immune reconsitution inflammatory syndrome (IRIS) that sometime occurs with initiation of effect antiretroviral therapy (ART). HL risk also has been associated with higher socioeconomic status and, specifically, with a hygienic childhood environment. To test this hygiene hypothesis a collaborative study is examining whether survivors of young adult HL have less diversity in their fecal microbiome compared to co-twin controls who have not developed HL. MCC is a rare but highly aggressive malignancy of neuro-endocrine cells that reside in the dermis. As MCC risk is increased with HIV/AIDS and with other immune deficiencies, pilot studies have been launched primarily to understand how MCC relates to the newly discovered Merkel cell polyomavirus (MCPyV). To explore the reduced risk of breast cancer for women with HIV/AIDS descriptive analyses have used data from the HIV AIDS Cancer Match and analytic analysis have used data and specimens from the Women's HIV Interagency Study and the HIV Epidemiology Research Study. In addition, as postmenopausal breast cancer (as well as endometrial cancer and perhaps colon cancer) is closely tied to elevated levels of systemic estrogens, studies have been initiated to test whether non-ovarian systemic estrogen levels are related to differences in fecal microbes and particularly to microbial beta-glucuronidase activity that deconjugates estrogen bile salts, enabling the free hormones to reabsorbed from the gut.